Bridge Funding for Dominantly Inherited Alzheimer Network

Washington University, Saint Louis MO

Investigators

Linked publications & trials

Abstract

Project Summary (DIAN Supplement) This application is for bridge funding until a resubmission can be reviewed and funded maintaining fundamental Core operations of the Dominantly Inherited Alzheimer Network (DIAN). The eight Cores of DIAN are: Administration, Clinical, Biostatistics, Neuropathology, Biomarker, Genetics, Imaging, and Cognition. The renewal application’s first year was budgeted for $13.1 million (total), and this supplement application reduces the year’s funding by $4.2 million to $8.9 million (total) to maintain the essential operations of the study which without would halt the availability of longitudinal data and resources to the scientific community or even dissolve the entirety of the program. Bridge funding would allow for 16 sites supported through DIAN to maintain study visits for its current active population of over 300 participants and provide the Coordinating Center the ability to continue managing the study; support performances sites; ensure validation and integrity to data collection, collect, manage, and handle data/tissue; and disseminate findings and study resources to the research and medical communities. To reduce funding support, this supplement halts all scientific project activities, limits travel costs to Coordinating Center Core members, delays home health nurse visits for non-U.S. sites in collecting assessments and specimens, and removes in- person family conference meeting support to the DIAN Expanded Registry (DIAN EXR). Additionally, the ongoing DIAN-Trials Unit (DIAN-TU) Amyloid Removal Trial (ART), which has found the first clinical signs of prevention of Alzheimer's disease in the clinic is dependent on this DIAN observational study continuing. If gap funding is not provided, this 10 year seminal trial will be forced to stop short of demonstrating how to prevent Alzheimer's disease. Since its inception, the DIAN has led major scientific advances in the understanding of Alzheimer’s disease (AD) stages, cerebrospinal fluid and plasma biomarkers, mechanistic links to therapeutic targets, and enabled ground-breaking prevention and interventional trials. DIAN has helped define the sequence, timing, and magnitude of longitudinal AD biomarker changes decades before symptoms begin. This work directly led to the development and implementation of primary and secondary prevention trials for autosomal dominant AD (ADAD) and the validation of the amyloid-tau-neurodegeneration (ATN) criteria. In this current funding cycle, the DIAN updated the longitudinal progression from biochemical Aβ imbalances, through sequential tau phosphorylations, to the emergence of tau pathology with symptom onset. This tau staging signature of AD can now be tracked with specific biomarkers and was confirmed in “sporadic” late onset AD (LOAD).